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The hph ‐1 mouse: A model for dominantly inherited GTP‐cyclohydrolase deficiency
Author(s) -
Hyland Keith,
Gunasekara Richard S.,
MunkMartin Tracy L.,
Arnold Lauren A.,
Engle Todd
Publication year - 2003
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10695
Subject(s) - tetrahydrobiopterin , biopterin , tyrosine hydroxylase , gtp cyclohydrolase i , endocrinology , medicine , homovanillic acid , striatum , biology , chemistry , dopamine , serotonin , nitric oxide synthase , receptor , nitric oxide
Abstract Dominantly inherited guanosine triphosphate (GTP)‐cyclohydrolase deficiency, otherwise known as Segawa's disease or dopa‐responsive dystonia, has a wide spectrum of phenotypic expression ranging from asymptomatic to very severe. Penetrance is more frequent in women as compared with men, and there is a variable occurrence of diurnal variation in symptom intensity. Biochemical characterization of the disease has demonstrated lower cerebrospinal fluid levels of tetrahydrobiopterin (BH4), neopterin, and homovanillic acid and low levels of tyrosine hydroxylase protein in the striatum. To investigate the pathophysiology, we have begun to characterize biogenic amine and BH4 metabolism in the GTP cyclohydrolase deficient hph‐1 mouse. The data show low brain levels of BH4, catecholamines, serotonin, and their metabolites together with low levels of tyrosine hydroxylase protein within the striatum. The hph‐1 mouse therefore provides a good model system in which to study the human disease. Ann Neurol 2003;54 (suppl 6):S46–S48